James W. Janetka, Ph.D.

Associate Professor

Biochemistry and Molecular Biophysics

Lab Website
Publications (PubMed / NIH)

Office: 2614 Cancer Research
Phone: 314-362-0509
Email: janetkaj@wustl.edu
 

Research

The Janetka research group is studying therapeutic targets and cellular mechanisms in cancer and infectious disease. The overall focus of the lab is to interfere with key biological processes outside the cell, by inhibiting one or more key proteins, which are important in bacterial pathogenesis or tumor progression. We employ rational structure-based drug design and synthetic medicinal chemistry to develop peptide-based and small molecule inhibitors as chemical tools to help decipher mechanisms of disease. In one project we are developing glycoside-based antagonists of adhesins, such as FimH, FmlD, and PapG, in E. coli., which are essential for host-bacteria interactions in UTI. In another project, we are developing peptide-based and small molecule inhibitors of serine proteases, including HGFA, matriptase and hepsin, which post-translationally process the growth factor ligands of c-MET and RON receptor tyrosine kinases, both important in tumor progression and metastatic cancer. The long-term goal of our research is to identify preclinical candidate drugs as new and innovative medicines for treating patients with resistant infections and cancer.

jim janetka lab pic


Select Publications

Tyagi R., Maddirala A.R., Elfawal M., Fischer C., Bulman C.A., Rosa B.A., Gao X., Chugani R., Zhou M., Helander J., Brindley P.J., Tseng C.C., Greig I.R., Sakanari J., Wildman S.A., Aroian R., Janetka J.W., & Mitreva M. (2018). “Small Molecule Inhibitors of Metabolic Enzymes Repurposed as a New Class of Anthelmintics.” ACS Infect Dis. 2018 Jul 13;4(7):1130-1145. doi: 10.1021/acsinfecdis.8b00090. Epub 2018 May 14. (Abstract)

Rocha A.G., Franco A., Krezel A.M., Rumsey J.M., Alberti J.M., Knight W.C., Biris N., Zacharioudakis E., Janetka J.W., Baloh R.H., Kitsis R.N., Mochly-Rosen D., Townsend R.R., Gavathiotis E., & Dorn G.W. 2nd (2018). “MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A.” Science. 2018 Apr 20;360(6386):336-341. doi: 10.1126/science.aao1785. (Abstract)

Kalas V., Hibbing M.E., Maddirala A.R., Chugani R., Pinkner J.S., Mydock-McGrane L.K., Conover M.S., Janetka J.W., & Hultgren S.J. (2018). “Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection.” Proc Natl Acad Sci U S A. 2018 Mar 5. pii: 201720140. doi: 10.1073/pnas.1720140115. (Abstract)

James W. Janetka & Roseann M. Benson (2018). “Extracellular Targeting of Cell Signaling in Cancer: Strategies Directed at MET and RON Receptor Tyrosine Kinase Pathways” ISBN-13: 978-1119300182, ISBN-10: 1119300185 (Publisher)

Spaulding C.N., Klein R.D., Schreiber H.L. 4th, Janetka J.W., & Hultgren S.J. (2018). “Precision antimicrobial therapeutics: the path of least resistance?” NPJ Biofilms Microbiomes. 2018 Feb 27;4:4. doi: 10.1038/s41522-018-0048-3. eCollection 2018. (Abstract)

Yang B., Vasbinder M., Hird A.W., Su Q., Wang H., Yu Y., Toader D., Lyne P.D., Read J.A., Breed J., Ioannidis S., Deng C., Grondine M., DeGrace N., Whitston D., Brassil P., & Janetka J.W. (2018). “Adventures in Scaffold Morphing: Discovery of Fused Ring Heterocyclic Checkpoint Kinase 1 (CHK1) Inhibitors.” J Med Chem. doi: 10.1021/acs.jmedchem.7b01490. (Abstract)

Rutaganira F.U., Barks J., Dhason M.S., Wang Q., Lopez M.S., Long S., Radke J.B., Jones N.G., Maddirala A.R., Janetka J.W., El Bakkouri M., Hui R., Shokat K.M., & Sibley L.D. (2017). “Inhibition of calcium dependent protein kinase 1 (CDPK1) by pyrazolopyrimidine analogs decreases establishment and reoccurrence of central nervous system disease by Toxoplasma gondii.” J Med Chem. 2017 Dec 28;60(24):9976-9989. doi: 10.1021/acs.jmedchem.7b01192. Epub 2017 Oct 9. (Abstract)

Spaulding C.N., Klein R.D., Ruer S., Kau A.L., Schreiber H.L., Cusumano Z.T., Dodson K.W., Pinkner J.S., Fremont D.H., Janetka J.W., Remaut H., Gordon J.I., & Hultgren S.J. (2017). “Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist.” Nature. 2017 Jun 22;546(7659):528-532. doi: 10.1038/nature22972. Epub 2017 Jun 14. (Abstract)

Owusu B.Y., Thomas S., Venukadasula P., Han Z., Janetka J.W., Galemmo R.A. Jr., & Klampfer L. (2017). “Targeting the tumor-promoting microenvironment in MET-amplified NSCLC cells with a novel inhibitor of pro-HGF activation.” Oncotarget. 2017 May 29;8(38):63014-63025. doi: 10.18632/oncotarget.18260. eCollection 2017 Sep 8. (Abstract)

Mydock-McGrane L.K., Hannan T.J., & Janetka J.W. (2017). “Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn’s disease.” Expert Opin Drug Discov. 2017 Jul;12(7):711-731. doi: 10.1080/17460441.2017.1331216. Epub 2017 Jun 2. (Abstract)

Owusu B.Y., Galemmo R., Janetka J., & Klampfer L. (2017). “Hepatocyte Growth Factor, a Key Tumor-Promoting Factor in the Tumor Microenvironment.” Cancers (Basel). 2017 Apr 17;9(4). pii: E35. doi: 10.3390/cancers9040035. (Abstract)

Budelier M.M., Cheng W.W.L., Bergdoll L., Chen Z.W., Janetka J.W., Abramson J., Krishnan K., Mydock-McGrane L., Covey D.F., Whitelegge J.P., & Evers A.S. (2017). “Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.” J Biol Chem. 2017 Jun 2;292(22):9294-9304. doi: 10.1074/jbc.M116.773069. Epub 2017 Apr 10. (Abstract)

Budelier M.M., Cheng W.W., Bergdoll L., Chen Z.W., Abramson J., Krishnan K., Qian M., Covey D.F., Janetka J.W., & Evers A.S. (2017). “Click Chemistry Reagent for Identification of Sites of Covalent Ligand Incorporation in Integral Membrane Proteins.” Anal Chem. 2017 Feb 21;89(4):2636-2644. doi: 10.1021/acs.analchem.6b05003. Epub 2017 Feb 9. (Abstract)

Kalas V., Pinkner J.S., Hannan T.J., Hibbing M.E., Dodson K.W., Holehouse A.S., Zhang H., Tolia N.H., Gross M.L., Pappu R.V., Janetka J., & Hultgren S.J. (2017). “Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions.” Sci Adv. 2017 Feb 10;3(2):e1601944. doi: 10.1126/sciadv.1601944. eCollection 2017 Feb. (Abstract)

Mydock-McGrane L., Cusumano Z., Han Z., Binkley J., Kostakioti M., Hannan T., Pinkner J.S., Klein R.D., Kalas V., Crowley J., Rath N.P., Hultgren S.J., & Janetka J.W. (2016). “Antivirulence C-Mannosides as Antibiotic-Sparing, Oral Therapeutics for Urinary Tract Infections.” J Med Chem. 2016 Oct 27;59(20):9390-9408. Epub 2016 Oct 14. (Abstract)


Books

Extracellular Targeting of Cell Signaling in Cancer: Strategies Directed at MET and RON Receptor Tyrosine Kinase PathwaysExtracellular Targeting of Cell Signaling in Cancer: Strategies Directed at MET and RON Receptor Tyrosine Kinase Pathways, available from the publisher (Wiley), Amazon, Barnes & Noble, and other bookstores.